Wu, NanBaiocchi, LeonardoZhou, TianhaoKennedy, LindseyCeci, LudovicaMeng, FanyinSato, KeisakuWu, ChaodongEkser, BurcinKyritsi, KonstantinaKundu, DebjyotiChen, LixianMeadows, VikFranchitto, AntonioAlvaro, DomenicoOnori, PaoloGaudio, EugenioLenci, IlariaFrancis, HeatherGlaser, ShannonAlpini, Gianfranco2022-04-212022-04-212020-12Wu, N., Baiocchi, L., Zhou, T., Kennedy, L., Ceci, L., Meng, F., Sato, K., Wu, C., Ekser, B., Kyritsi, K., Kundu, D., Chen, L., Meadows, V., Franchitto, A., Alvaro, D., Onori, P., Gaudio, E., Lenci, I., Francis, H., … Alpini, G. (2020). Functional Role of the Secretin/Secretin Receptor Signaling During Cholestatic Liver Injury. Hepatology, 72(6), 2219–2227. https://doi.org/10.1002/hep.314840270-9139, 1527-3350https://hdl.handle.net/1805/28649Liver diseases are a major health concern and affect a large proportion of people worldwide. There are over 100 types of liver disorders, including cirrhosis, cholangiocarcinoma (CCA), hepatocellular carcinoma, and hepatitis. Despite the relevant number of people who are affected by liver diseases, and the increased awareness with regard to these disorders, the number of deaths corresponding to liver injury is expected to increase in the foreseeable future. One of the possible reasons for this is that a complete comprehension of the mechanisms of hepatic damage involving specific liver anatomical districts is lacking, and, as a consequence, current treatments available are suboptimal. A major burden in the clinical setting are chronic cholestatic liver diseases (e.g., primary biliary cholangitis [PBC], primary sclerosing cholangitis [PSC], biliary atresia), which target the biliary epithelium and are characterized by cholestasis.(1, 2) Because the secretin (Sct)/secretin receptor (SR) axis (expressed only by cholangiocytes in the liver)(3, 4) is the major regulator of ductal bile secretion,(5, 6) it is intuitive that this axis plays a key role in the maintenance of biliary homeostasis during the progression of cholangiopathies. For instance, PBC is characterized by reduced bicarbonate secretion, a phenomenon possibly impeding the formation of an HCO3 canalicular film (“bicarbonate umbrella”) on bile ducts, which has protective properties against highly concentrated bile acids (BAs).(1, 7, 8) In this review, we examined the molecular mechanisms by which the Sct/SR axis regulates biliary function and the homeostasis of the biliary epithelium in normal and pathophysiological conditions.en-USPublisher PolicySecretinLiver InjurySecretin receptorArticle